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Protection against lethal subcutaneous challenge of virulent Y. pestis strain 141 using an F1-V subunit vaccine
Authors:Wang Dong  Jia Nuan  Li Peng  Xing Li  Wang XiLiang
Affiliation:1. Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China
2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3. Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China;Hospital Attached to Aeromedicine Institute of PLA, Beijing 100089, China
Abstract:In this study, we designed and engineered a two-component recombinant fusion protein antigen as a vaccine candidate against the possible biological threat of Yersinia pestis. The recombinant F1-V protein was formulated with Alhydrogel. A four-time injection with a dosage of 10, 20 and 50 μg/mouse in about two months was adopted for vaccination. Serum antibodies and subclass of T helper cells were measured and analyzed. After the final vaccination, the mice were challenged by 141 strain with 25–600 LD50. In conclusion, the recombinant vaccine was capable of inducing protective immunity against subcutaneous challenge. The level of serum IgG was supposed to be a main factor that affected the final protection of challenge. 20 μg recombinant protein could induce an endpoint titre of serum IgG as high as 51200, which was enough to afford 100% protection against 400 LD50 virulent 141 challenge. The antibody isotype analysis showed that the vaccine induced predominantly an IgG1 rather than IgG2a response. Flow cytometric analysis revealed that Alhydrogel significantly helped induce a stronger humoral immunity instead of CTL cellular response. These findings suggested that the plague F1-V subunit vaccine is promising for the next plague vaccine.
Keywords:Yersinia pestis  F1-V fusion protein  challenge  subunit vaccine
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